title: The β-carboline alkaloid harmine inhibits telomerase activity of MCF-7 cells by down-regulating hTERT mRNA expression accompanied by an accelerated senescent phenotype.
abstract: The end replication problem, which occurs in normal somatic cells inducing replicative senescence, is solved in most cancer cells by activating telomerase. The activity of telomerase is highly associated with carcinogenesis which makes the enzyme an attractive biomarker in cancer diagnosis and treatment. The indole alkaloid harmine has multiple pharmacological properties including DNA intercalation which can lead to frame shift mutations. In this study, harmine was applied to human breast cancer MCF-7 cells. Its activity towards telomerase was analyzed by utilizing the telomeric repeat amplification protocol (TRAP). Our data indicate that harmine exhibits a pronounced cytotoxicity and induces an anti-proliferation state in MCF-7 cells which is accompanied by a significant inhibition of telomerase activity and an induction of an accelerated senescence phenotype by over-expressing elements of the p53/p21 pathway.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute , La Jolla, CA , USA ; Institute of Pharmacy and Molecular Biotechnology, Heidelberg University , Heidelberg , Germany.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
keywords: Alkaloid; Apoptosis; DNA intercalation; MCF-7; Senescence; Telomerase; p21; p53